Breast cancer research has traditionally focused on biological females who identify as women. Less is known about the incidence of breast cancer in transgender populations who identify with a gender that does not correspond with their birth sex. There are data to suggest a potential link between hormone replacement therapy (HRT) and breast cancer in transgender patients. While there is a need for more robust studies in this area, current data suggest there is no increased risk in female-to-male transgender men, and a potential increased risk in male-to-female transgender women. These studies also suggest that transgender patients face significant disparities in care. Clinicians require improved education to understand the potential risks associated with HRT, standards of cancer screening for transgender patients, and proper sensitivity in communication with this patient population. This review examines the existing literature, outlines the current data on the potential risks associated with HRT, and provides a 3-pronged approach to communicate risk, screen, and diagnose breast cancer in transgender patient populations. Note: All authors contributed equally to this manuscript.